Valencia

Researchers are evaluating remibrutinib (LOU064) in adolescents aged 12 to under 18 years who have chronic spontaneous urticaria (CSU) that is not well controlled by H1-antihistamines. This Phase 3 trial aims to assess the effectiveness, how the drug is processed in the body, and safety of remibrutinib compared to a placebo. The study also intends to gather long-term data on how well remibrutinib works and its safety over several years after treatment ends. The trial includes three periods. First, the core period is a 24-week double-blind phase where about two-thirds of participants receive remibrutinib and one-third receive placebo, with about 10 site visits over approximately 32 weeks. Next is an optional open-label extension lasting from one to three years, where participants who completed the core period may receive remibrutinib or enter an observational treatment-free phase depending on their symptoms. Participants may cycle through treatment and observational periods up to six times. Finally, an optional long-term treatment-free follow-up can last up to three years with one site visit and up to four phone calls. During the study, participants undergo assessments including changes in urticaria activity scores (UAS7), itching severity (ISS7), and hive severity (HSS7) measured from baseline to 12 weeks. Regular visits monitor safety, symptoms, and drug effects. The study tracks these measures to understand remibrutinib's impact on CSU symptoms and overall safety profile during and after treatment, with total participation potentially lasting several years.

Preterm birth before 37 weeks' gestation is common and linked to many health challenges, especially when it occurs before 29 weeks. At this early stage, infants often face breathing difficulties due to immature lungs, sometimes requiring resuscitation. This study aims to compare two oxygen concentrations, 30% and 60%, used during resuscitation of very preterm infants to determine which leads to better survival and neurodevelopmental outcomes by about two years of age. The study uses a cluster randomized crossover design, where hospitals alternate between using 30% and 60% oxygen to resuscitate infants born between 23 and 28 weeks gestation. Infants receive the assigned oxygen concentration for the first 5 minutes after birth, with adjustments made based on oxygen saturation levels to maintain safe ranges. The intervention lasts 10 minutes, including initial resuscitation and oxygen titration to stabilize the infant. Participants will be closely monitored during their hospital stay and followed up at 24 months corrected age to assess survival and major neurodevelopmental outcomes. Data collected will include oxygen saturation, heart rate during resuscitation, and longer-term health measures. The study's results aim to guide safer oxygen use in resuscitating extremely preterm infants worldwide.

Chronic kidney disease (CKD) affects over 800 million people worldwide and leads to high health burdens, multiple related diseases, frequent doctor visits, hospitalizations, and significant healthcare costs. New drug treatments like sodium-glucose co-transporter 2 inhibitors, finerenone, and semaglutide have shown promise in lowering albuminuria and protecting kidney function, but the best way to combine or sequence these treatments is unclear. This study aims to evaluate if using biomarkers to guide treatment choices can better slow kidney function decline compared to standard care in people with CKD and albuminuria. This is a Phase 4, prospective, randomized, open-label, parallel-group, multicenter study enrolling 125 adults with CKD who have an estimated glomerular filtration rate (eGFR) of at least 25 mL/min/1.73m2 and urinary albumin-to-creatinine ratio (UACR) between 100 and 5000 mg/g. Participants are randomly assigned to either a biomarker-targeted treatment approach or standard care. In the biomarker group, patients start treatment with one of three drugs (dapagliflozin, finerenone, or semaglutide) and after about four weeks on the maximum tolerated dose, urinary biomarkers are measured to decide whether to continue, switch, or add another drug. This process can repeat up to three drugs based on biomarker responses. Participants will be monitored for changes in kidney function primarily by measuring the chronic eGFR slope from week 26 to 104. Throughout the study, urine samples for biomarkers and clinical assessments will be conducted to track treatment effects. Safety and adherence will be evaluated, and the study duration includes regular follow-ups to assess long-term impacts of the biomarker-guided treatment compared to standard care.

Researchers are studying advanced renal cell carcinoma (RCC) that has returned after prior adjuvant therapy. The trial aims to find out if treatment with belzutifan and zanzalintinib helps patients live longer and delays disease progression compared to treatment with cabozantinib. This is a Phase 3 randomized study focusing on participants with recurrent advanced RCC who have previously received anti-PD-1/L1 therapy. Participants are randomly assigned to receive one of two oral drug regimens: either belzutifan combined with zanzalintinib, both taken once daily, or cabozantinib alone, also taken once daily. The study compares these treatments to assess their effects on disease control and overall survival. During the study, participants will be monitored for progression-free survival and overall survival for up to approximately 73 months. Researchers will evaluate how well the cancer responds to treatment and track any changes in health status over time. Safety and effectiveness of the treatments will be closely followed throughout the study period.

Researchers are studying whether combining calderasib, a targeted therapy for the KRAS G12C mutation, with subcutaneous pembrolizumab can treat non-small cell lung cancer (NSCLC). The study aims to determine if people receiving calderasib with pembrolizumab live longer without their cancer growing or spreading compared to those receiving pembrolizumab with chemotherapy. This is a phase 3, randomized, open-label, multicenter clinical trial focusing on participants with advanced or metastatic nonsquamous NSCLC carrying the KRAS G12C mutation. Participants will receive one of two treatment combinations. One group will take calderasib orally along with subcutaneous pembrolizumab and berahyaluronidase alfa injections. The other group will receive subcutaneous pembrolizumab combined with chemotherapy drugs pemetrexed and a platinum-based drug, either carboplatin or cisplatin, administered by intravenous infusion. These treatments are given as first-line therapy, and the study evaluates their safety and effectiveness. During the study, researchers will monitor participants for progression-free survival, especially focusing on those with at least 1% PD-L1 tumor proportion score, for up to approximately 48 months. Participants will undergo regular assessments to track cancer progression and response to treatment. Safety and efficacy data will be collected throughout the study to understand how well the treatments work and their side effects over time.

Researchers are evaluating new treatment options for adults with locally advanced or metastatic colorectal cancer that cannot be removed by surgery and has a specific KRAS G12C gene mutation. This study compares the safety and effectiveness of adding calderasib and cetuximab, both targeted therapies, to a standard chemotherapy regimen called mFOLFOX6. The goal is to see if this combination can help patients live longer without their cancer growing or spreading compared to current treatments that may include mFOLFOX6 with or without bevacizumab. The study has two parts. It involves treatment with calderasib taken as an oral tablet, cetuximab given according to standard procedures, and mFOLFOX6 chemotherapy combining oxaliplatin, leucovorin/levofolinate calcium, and 5-fluorouracil. Some participants may receive bevacizumab or a bevacizumab biosimilar as part of the comparison. The treatments are given following approved dosing schedules. This design allows researchers to assess the safety and tolerability of these drug combinations in treating this type of colorectal cancer with the KRAS G12C mutation. Participants will be monitored for side effects, treatment tolerability, and cancer progression over a period that may last up to about 44 months. Researchers will track outcomes such as how many participants experience dose-limiting toxicities or adverse events, how many stop treatment due to side effects, and progression-free survival time. Assessments include health evaluations, laboratory tests, and imaging to observe cancer status. This long-term follow-up aims to understand both safety and effectiveness of the treatment combinations.

Researchers are evaluating a new treatment called ifinatamab deruxtecan (I-DXd) for men with metastatic castration-resistant prostate cancer (mCRPC). This study compares I-DXd to chemotherapy to see if it helps people live longer overall and live longer without their cancer worsening. It is a Phase 3, open-label trial focused on patients who have progressed on prior therapies and have evidence of metastatic disease. Participants receive either I-DXd through an intravenous infusion every 3 weeks or docetaxel chemotherapy administered every 3 weeks. Prednisone tablets are also given daily as part of the treatment plan. Before each I-DXd dose, premedication is provided to help prevent nausea and vomiting using a combination of drugs such as corticosteroids and anti-nausea medicines. Treatment continues until disease progression, unacceptable side effects, or other reasons to stop. During the study, researchers monitor overall survival and how long patients live without their cancer progressing, for up to about 36 months. Participants undergo tumor tissue collection, scans, and assessments to track disease status and side effects. Safety is closely watched throughout treatment. The study includes men aged 18 and older with confirmed prostate cancer and metastatic disease who have previously received certain hormone therapies but no prior taxane chemotherapy for mCRPC.

Researchers are studying a new treatment for HIV-1 infection that combines two medicines, islatravir and ulonivirine, taken once weekly. The goal is to see if this new study treatment works as well as the standard antiretroviral therapy (ART), which usually involves taking up to three medicines once or twice daily. This research also aims to learn about the safety and tolerability of the study treatment compared to the standard ART. The study compares the once-weekly combination of islatravir and ulonivirine with the standard daily treatment of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). Participants will take either the study drugs or the standard drugs for 96 weeks. Some participants may receive matching placebos as part of the study design. The treatment is given orally as capsules or tablets according to the assigned group. Participants will be monitored throughout the study with regular assessments, including measuring the amount of HIV-1 virus in the blood to see if it is suppressed below 50 copies/mL at weeks 24 and 48. The study will also track any side effects or adverse events and whether participants stop the treatment due to these events. Overall, the study lasts about 96 weeks, with ongoing safety and effectiveness evaluations to understand how well the treatments work and how safe they are over time.

Researchers are evaluating new treatment options for women with relapsed high-grade serous ovarian cancer, a fast-growing cancer that starts in the cells covering the ovaries, lining of the belly, or fallopian tubes. This study focuses on people whose cancer has returned after prior platinum-based chemotherapy. The goal is to assess the safety, tolerability, and effectiveness of a new antibody drug conjugate called raludotatug deruxtecan (R-DXd), alone or combined with other anticancer treatments, in this patient group. The study has two parts: Part 1 is a dose escalation phase to find the recommended dose of R-DXd, and Part 2 is an expansion phase using that dose. R-DXd is given as an intravenous infusion on Day 1 of every 3-week cycle. Other treatments that may be given include carboplatin and paclitaxel (each up to 6 cycles), bevacizumab every 3 weeks, pembrolizumab up to 35 cycles, gemcitabine on Days 1 and 8 of each 3-week cycle, and pegylated liposomal doxorubicin every 4 weeks. Rescue medications to control side effects are also administered according to protocol. Participants will be monitored for adverse events, dose-limiting toxicities, and treatment discontinuations up to about 3 years. Researchers will measure cancer response using established criteria and assess safety through clinical exams, imaging, and laboratory tests. Eligibility includes having measurable disease and adequate health status. The study includes long-term follow-up to track treatment effects and safety outcomes over time.

Researchers are investigating new treatments for metastatic cervical cancer, which is cancer that has spread from the cervix to other parts of the body. This Phase 3 study aims to evaluate the safety and effectiveness of combining sacituzumab tirumotecan (sac-TMT), an antibody drug that targets cancer cells, with pembrolizumab and bevacizumab. The study seeks to find out if this combination can help people live longer or keep their cancer from worsening compared to standard treatments. The study has two parts. In Part 1, participants receive sac-TMT together with pembrolizumab and bevacizumab to assess safety. In Part 2, after standard initial treatment, those whose cancer does not progress will be randomly assigned to maintenance treatment with either pembrolizumab alone or sac-TMT plus pembrolizumab. Bevacizumab may be added during maintenance treatment based on the doctor's decision. All treatments are given through intravenous infusions, and participants may receive rescue medications to manage side effects before sac-TMT infusion. Participants will be monitored for adverse events and treatment tolerability over several months. The study measures include progression-free survival and overall survival, assessed by independent review. Safety and treatment continuation rates are tracked during Part 1 for up to approximately 66-69 months, while Part 2 outcome measures extend up to 48-60 months. Various assessments, including laboratory tests and evaluations of cancer status, will be performed throughout the study to understand treatment effects and participant well-being.